TY - JOUR
T1 - Loss of Tie2 receptor compromises embryonic stem cell-derived endothelial but not hematopoietic cell survival
AU - Hamaguchi, Isao
AU - Morisada, Tohru
AU - Azuma, Masaki
AU - Murakami, Kyoko
AU - Kuramitsu, Madoka
AU - Mizukami, Takuo
AU - Ohbo, Kazuyuki
AU - Yamaguchi, Kazunari
AU - Oike, Yuichi
AU - Dumont, Daniel J.
AU - Suda, Toshio
PY - 2006/2/1
Y1 - 2006/2/1
N2 - Tie2 is a receptor-type tyrosine kinase expressed on hematopoietic stem cells and endothelial cells. We used cultured embryonic stem (ES) cells to determine the function of Tie2 during early vascular development and hematopoiesis. Upon differentiation, the ES cell-derived Tie2 +Flk1+ fraction was enriched for hematopoietic and endothelial progenitor cells. To investigate lymphatic differentiation, we used a monoclonal antibody against LYVE-1 and found that LYVE-1+ cells derived from Tie2+Flk1+ cells possessed various characteristics of lymphatic endothelial cells. To determine whether Tie2 played a role in this process, we analyzed differentiation of Tie2-/- ES cells. Although the initial numbers of LYVE-1+ and PECAM-1 + cells derived from Tie2-/- cells did not vary significantly, the number of both decreased dramatically upon extended culturing. Such decreases were rescued by treatment with a caspase inhibitor, suggesting that reductions were due to apoptosis as a consequence of a lack of Tie2 signaling. Interestingly, Tie2-/- ES cells did not show measurable defects in development of the hematopoietic system, suggesting that Tie2 is not essential for hematopoietic cell development.
AB - Tie2 is a receptor-type tyrosine kinase expressed on hematopoietic stem cells and endothelial cells. We used cultured embryonic stem (ES) cells to determine the function of Tie2 during early vascular development and hematopoiesis. Upon differentiation, the ES cell-derived Tie2 +Flk1+ fraction was enriched for hematopoietic and endothelial progenitor cells. To investigate lymphatic differentiation, we used a monoclonal antibody against LYVE-1 and found that LYVE-1+ cells derived from Tie2+Flk1+ cells possessed various characteristics of lymphatic endothelial cells. To determine whether Tie2 played a role in this process, we analyzed differentiation of Tie2-/- ES cells. Although the initial numbers of LYVE-1+ and PECAM-1 + cells derived from Tie2-/- cells did not vary significantly, the number of both decreased dramatically upon extended culturing. Such decreases were rescued by treatment with a caspase inhibitor, suggesting that reductions were due to apoptosis as a consequence of a lack of Tie2 signaling. Interestingly, Tie2-/- ES cells did not show measurable defects in development of the hematopoietic system, suggesting that Tie2 is not essential for hematopoietic cell development.
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U2 - 10.1182/blood-2005-05-1823
DO - 10.1182/blood-2005-05-1823
M3 - Article
C2 - 16219799
AN - SCOPUS:31544456613
VL - 107
SP - 1207
EP - 1213
JO - Blood
JF - Blood
SN - 0006-4971
IS - 3
ER -